151751-Najiba-Chargi

237 Systemic therapy: skeletal muscle mass and anti-cancer drug toxicity INTRODUCTION There is a high prevalence of low skeletal muscle mass (SMM), sometimes referred to as sar - copenia, in cancer patients. Moreover, in advanced stages of cancer, the majority of patients exhibit low SMM. 1,2 A large number of studies has been performed to investigate the predictive value of low SMM. Especially, the association between low SMM and survival has been thor - oughly investigated. 2–4 This prognostic value of low SMM has been demonstrated in a variety of cancer types including lung 3 , colorectal 5 , breast 6 , renal 7 , and head and neck cancer 8 . Low SMMhas also been investigated as a predictive factor for adverse events such as chemotherapy toxicity, surgical complications, and radiotherapy toxicity. 5–7,9,10 There are several techniques for the measurement of skeletal muscle mass (SMM). This in - cludes dual-energy X-ray absorptiometry (DXA), which uses x-rays that will reduce in energy based on the composition and thickness of the material that it passes through, and bioelectric impedance analysis (BIA), which measures body composition using an electrical current that experiences more resistance through adipose tissue as opposed to electrolyte-rich fluids. 7,11 The most commonly used technique utilizes computed tomography (CT) as it is part of routine care in themajority of cancer patients, and it has a proven high accuracy inmeasuring SMM. 3,8,12 Most studies quantify SMM using CT scans of the third lumbar (L3) vertebrae, although other levels have also been used. The cross-sectional area (CSA) of skeletal musclemass is measured on a single cross-sectional image and normalized for height resulting in the skeletal muscle mass index (SMI). The SMI correlates strongly with total-body skeletal musclemass. 12,13 Recent- ly, magnetic resonance imaging (MRI) has been proven to have a strong correlation (r 2 =0.94, p<0.01) with CT for the measurement of the CSA of SMM. 14 Although the predictive value of low SMM has been investigated frequently, the underlying mechanism is only hypothesized. There are theories about the underlying pathophysiology of low SMM such as the influence of age, intracellular oxidative stress, and genetic compo- nents. 3,15 In cancer patients, there is also a high possibility of developing cachexia which could also result in low SMM. 3,15 There are several theories for the mechanism by which low SMM influences toxicity. Some theorize that the altered ratio of fat-to-lean body mass can influence the pharmacokinetics of anti-cancer drugs. 11 Others theorize that low SMM is independently associated with frailty, which can result in a higher risk of adverse events. 4,11,16 The most com- monly supported hypothesis is based on the influence of low SMM on drug distribution. The body consists of two major compartments, fat mass (FM) and lean body mass (LBM); drugs can be inclined to distribute towards one of these compartments. Patients with low SMM have a decreased LBM and, as muscle mass is the largest contributor to LBM, this may result in increased drug levels in the plasma and thereby a higher risk of toxicity. 6,8,11,17 Although there have been many studies devoted to the predictive value of low SMM for an- ti-cancer drug toxicity, these studies have several limitations, such as small sample sizes. Additionally, the majority of studies focus on a single cancer type or disease stage which limits 13